17q12 Recurrent Duplication

Clinical characteristics: The 17q12 recurrent duplication is characterized by intellectual abilities ranging from normal to severe disability and other variable clinical manifestations. Speech delay is common, and most affected individuals have some degree of hypotonia and gross motor delay. Behavioral and psychiatric conditions reported in some affected individuals include autism spectrum disorder, schizophrenia, and behavioral abnormalities (aggression and self-injury). Seizures are present in 75%. Additional common findings include microcephaly, ocular abnormalities, and endocrine abnormalities. Short stature and renal and cardiac abnormalities are also reported in some individuals. Penetrance is incomplete and clinical findings are variable.

Diagnosis/testing: The diagnosis is established in a proband by detection of the 1.4-megabase heterozygous recurrent duplication at chromosome 17q12 by chromosomal microarray testing or other genomic methods.

Management: Treatment of manifestations: Those with developmental delays, cognitive disability, and/or behavioral issues should be evaluated by a neurodevelopmental pediatrician or clinical psychologist/psychiatrist. Seizures should be managed by a neurologist using standard practice. Feeding therapy as needed. Individuals with vision, endocrine, cardiac, and/or renal abnormalities should be managed by the appropriate specialist.

Surveillance: Regular assessment of psychomotor development is recommended for all children with the 17q12 recurrent duplication as well as psychological evaluation in both affected children and adults. Monitor for new-onset seizures, growth and nutritional assessment, and assessment of family needs at each visit.

Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in at-risk relatives to identify as early as possible those who would benefit from close assessment/monitoring of developmental milestones in childhood or psychological assessment/intervention through adulthood.

Genetic counseling: The 17q12 recurrent duplication is inherited in an autosomal dominant manner, with approximately 10% of duplications occurring de novo and approximately 90% inherited from a parent who is often minimally affected or phenotypically normal. Prenatal testing for an at-risk pregnancy requires prior identification of the duplication in an affected family member. Interpretation of results from prenatal testing is challenging given the inherent difficulty in accurately predicting the phenotype.